Risk for Death Significantly Increased in Patients With Synucleinopathies

Patients with synucleinopathies face at least a 2-fold greater risk for death than the general population.

Patients diagnosed with synucleinopathies have a higher risk for death than the general population, according to data published in JAMA Neurology. Multiple system atrophy with parkinsonism (MSA-P), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD) all increased risk for mortality significantly by more than 2-fold compared with in age and sex-matched control patients, whereas mortality risk was increased 1.75-fold in Parkinson's disease (PD) alone.

Using the Rochester Epidemiology Project medical records linkage system, a team of investigators from the Mayo Clinic identified a cohort of 461 patients diagnosed with synucleinopathies between 1991 and 2010 from Olmsted County, Minnesota. The majority of the participants (309, 67%) were diagnosed with PD, whereas the rest included 81 (17.6%) with DLB, 55 (11.9%) with PDD, and 16 (3.5%) with MSA-P. A second group of 452 "referent" control participants (9 of whom died before data collection) were then matched patient by patient.

Sixty percent of all participants were male, and women outlived the men by a median difference of 2.3 years among cohort patients and 2.2 years among the referent controls. The median age at onset of parkinsonian symptoms was 75.8 years (interquartile range, 67.4-81.7 years), and the median age at death was 84.7 years (interquartile range, 79.3-89.7 years). Among the referent participants, median age at onset for the corresponding patient was the same, but the median age at death was later, at 87.8 years.

The cause of death was known in more than 98% of all cases. Neurodegenerative disease was the most frequent cause of death among patients with synucleinopathies (31.5%), followed by cardiovascular events (15.8[ALH1] %) and respiratory failure/pneumonia (15.4%). Among the referents, the most common causes of death were cardiovascular events (25.5%) and cancer (18.1%). The authors observed a pattern consistent with a suspected inverse relationship between normal comorbidities of aging, particularly cancer, and neurodegenerative disorders.

Two thirds (68.6%, n=316) of the patient cohort died during the 10-year study follow-up compared with 48.7% (n=220) of the referent controls. The highest risk for death was among patients with MSA-P (hazard ratio [HR], 10.51; 95% CI, 2.92-37.82), followed by DLB (HR, 3.94; 95% CI, 2.61-5.94), PDD (HR, 3.86; 95% CI, 2.36-6.30), and PD (HR, 1.75; 95% CI, 1.39-2.21). Mortality occurred 6, 4, and 3.5 years earlier, respectively, in MSA-P, DLB, and PDD than among referents. Death from PD occurred only 1 year earlier than in the referent controls.

The findings from the current study were largely consistent with general findings indicating shorter survival in MSA-P. Ultimately, there was a 10-fold higher increased risk for death in MSA-P compared with PD, which had the lowest increase in mortality of the synucleinopathies.